Detection of Metastatic Lesions in Esophageal Cancer Using a TROP2 Antibody‐Based Near‐Infrared Probe

ABSTRACT Sacituzumab govitecan (SG), a trophoblast cell surface antigen 2 (TROP2)‐targeting antibody‐drug conjugate, is effective against solid tumors and a promising carrier for molecular imaging, yet its role in near‐infrared (NIR) fluorescence imaging of metastases is unclear. Based on the dual rationale of frequent lymph node metastasis in esophageal squamous cell carcinoma (ESCC) and prevalent TROP2 overexpression, the IRDye800cw‐labeled SG probe (SG‐IR800) was evaluated for detecting metastases of ESCC. Cellular uptake of SG was significantly higher in TROP2‐positive KYSE150 cells than in TROP2‐negative EC109 cells. Both subcutaneous KYSE150 tumors and patient‐derived xenograft models with high TROP2 expression demonstrated significantly higher accumulation of SG‐IR800 compared to the control probe. Peritoneal metastases yielded an NIR signal in the second window (NIR‐II) comparable to primary tumors, which outperformed the NIR‐I signal. Metastatic lymph nodes showed higher NIR‐II contrast than inflammatory nodes. This study demonstrates that the SG‐IR800 probe possesses high specificity for TROP2‐positive ESCC, facilitates the detection of metastatic lesions, and holds strong potential for guiding precise intraoperative navigation.